How the pandemic swine flu virus came to be

The new H1N1 strain is based primarily on an influenza virus that has been spreading in U.S. pigs since the mid-1990s.

The virus behind the current influenza pandemic may be known as swine flu, but it didn't come only from pigs. Wild birds and humans also played a role in its creation. Scientists are still trying to unravel how it wound up infecting people and spreading rapidly around the globe. Here's what they know so far.

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What's the lineage of H1N1?

The new H1N1 strain is based primarily on an unusual influenza virus that has been circulating widely in U.S. pigs since the mid-1990s. That "triple reassortant" flu is actually a combination of classical swine flu, a North American avian flu, and a strain of human flu. Somehow, a single pig became simultaneously infected with that virus and a pure swine flu strain found in pigs in Europe and Asia. The two strains swapped genetic material to produce the new H1N1 strain, which then began to infect humans.

By comparing the small genetic differences in flu samples from many patients, scientists estimate the pandemic strain was already circulating in people by November 2008. The earliest cases to be confirmed in people occurred in Mexico in March.

How did the two strains of swine flu mix?

That remains a mystery, and scientists will probably never know. Relatively few pigs engage in intercontinental travel, and those that do are strictly quarantined.

But there are theories. One is that a person in Asia became infected with the Eurasian swine flu, then traveled to North America and passed it along to a pig here that already had the triple reassortant virus. That would explain why the outbreak began in Mexico and the United States.

Another theory holds that an infected North American pig traveled to Asia and passed along its virus to another pig with the Eurasian flu strain. That pig then infected a person, who brought the virus back to North America and spread it to other people. This would explain why H1N1 has seven out of eight genes in common with a flu sample taken from a Hong Kong pig in 2004.

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Why is it so easy for flu strains to mix and match?

When a flu virus infects a cell, it breaks down into its eight component genes and invades the cell's nucleus. Once inside, those genes make hundreds of copies of themselves. Then they exit the nucleus and repackage themselves into new flu particles, which go on to infect additional cells. If a single cell is infected with two strains of flu at the same time -- which can happen easily -- genes from both can be bundled together to form a new virus.

Two of those genes are particularly important -- the ones that make the hemagglutinin (H) and neuraminidase (N) proteins. Hemagglutinin allows invading flu particles to attach to a host cell, and neuraminidase lets new flu particles detach from the host and find new cells to attack. If a new virus has a never-before-seen combination of these proteins, people won't have any immunity and a pandemic can result.

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Why is it often referred to with an A, as in (A)H1N1?

It's a sub-type within the A group of influenza viruses. There are three types of flu viruses - influenza A, influenza B and influenza C. There is the greatest variety among influenza A viruses, in part because they can infect many animal species. As a result, they are the only ones dangerous enough to cause severe disease or pandemics. The seasonal flu shot protects against two different strains of influenza A, along with one strain of influenza B. The B viruses mutate much more slowly and rarely infect animals other than humans. With their limited genetic diversity, they don't pose a pandemic threat. Influenza C viruses are relatively uncommon. They can sicken humans, dogs and pigs, and typically cause only mild illness in children.

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Haven't there been other H1N1s before?

Yes. The 1918 Spanish flu was an H1N1 strain, and one of the dominant strains of the seasonal flu is also an H1N1. But not all H1s and N1s are the same. The hemagglutinin in the current pandemic strain came from classical swine flu, and the neuraminidase is from the Eurasian swine flu. The H1 and N1 in the seasonal flu are both from humans. But the main reason why the new H1N1 is so much more virulent is that most people have never encountered it before, so they have no pre-existing immunity.

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Is the pandemic strain of H1N1 more deadly than the seasonal flu?

It doesn't seem to be, but it's hard to say for sure. Public health officials keep track of how many people have died from H1N1, but without reliable figures on how many people have been infected, they don't know for sure what proportion of cases result in death.

In May, an international group of researchers analyzed the outbreak in Mexico and concluded the fatality rate there was 0.4%. About a week later, Dr. Anne Schuchat of the Centers for Disease Control and Prevention in Atlanta said the fatality rate of H1N1 was "likely a little bit higher" than for the seasonal flu. The CDC estimates that seasonal flu contributes to 36,000 deaths in the U.S. each year, and the mortality rate varies between 0.06% and 0.24%.